AbstractBackground: Platinum-based chemotherapy is important for the treatment for recurrent or metastatic nasopharyngeal carcinomas (RM-NPCs). However, the prognosis of RM-NPC patients remains poor. This study evaluated the efficacy and safety of vascular-targeting agentsplus chemotherapy for RM-NPC treatment. Methods: This observational clinical trial, conducted at seven hospitals in Guangxi between January 2017 and December 2021, included 198 patients (158 males [79.8%]; median age, 51 years [IQR, 45–57years]). Chemotherapy was administered with and without vascular-targeting agents in 66 and 132 patients, respectively. The primary endpoint was progression-free survival (PFS), assessed by a blinded independent review committee according to RECIST v.1.1. The secondary end points were overall survival (OS) and safety. Results: After a median follow-up of 20 months, 31 (47.0%) and 82 (62.1%) deaths occurred in the combination therapy and chemotherapy alone groups, respectively. Median PFS was significantly higher in the combination group (7.0 months [95% CI, 5.7–8.3 months]) than in the chemotherapy alone group (5.0 months [95% CI, 4.1–5.9 months], P = 0.034), with a hazard ratio of 0.73 (95% CI, 0.54–0.98). The combination group exhibited a higher median OS compared to the chemotherapy alone group (37 months [95% CI, 21.3–52.7] vs. 20 months [95% CI, 13.0–27.0months], P = 0.047), representing a hazard ratio of 0.66 (95% CI, 0.45–0.97). In the combination therapy group, the most common adverse events were hypertension (n = 10/66 [15.1%]). Conclusion: The addition of vascular-targeting agents to chemotherapy for RM-NPC patients provided superior efficacycompared to chemotherapy alone, along with a manageable safety profile.
Prostate cancer (PCa) is one of the most common malignancies in men worldwide, and metastatic castrate-resistant prostate cancer (mCRPC) has shown a poor prognosis. Although chemotherapy and androgen deprivation therapy (ADT) have improved clinical outcomes, the median survival (MS) of patients with mCRPC is still less than 2 years. With the development of poly adenosine diphosphate-ribose polymerase inhibitor (PARPi), the treatment strategy for patients with mCRPC has markedly evolved. Olaparib, a type of PARPi that can selectively induce synthetic lethality in cancer cells with homologous recombination (HR) deficiencies, was the first type of PARPi approved for treating patients with mCRPC harboring mutations in HR repair (HRR) genes. This review discusses and summarizes the latest progress on therapeutic mechanisms, monotherapy, combination therapy, and adverse events of Olaparib.
Northwest Xizang White Cashmere Goat (NXWCG) is the first new breed of cashmere goat in the Xizang Autonomous Region. It has significant characteristics of extremely high fineness, gloss, and softness. Genome-wide association analysis is an effective biological method used to measure the consistency and correlation of genotype changes between two molecular markers in the genome. In addition, it can screen out the key genes affecting the complex traits of biological individuals. The aim of this study was to analyze the genetic mechanism of cashmere trait variation in NXWCG and to discover SNP locus and key genes closely related to traits such as superfine cashmere. Additionally, the key genes near the obtained significant SNPs were analyzed by gene function annotation and biological function mining. In this study, the phenotype data of the four traits (cashmere length, fiber length, cashmere diameter, and cashmere production) were collected. GGP_Goat_70K SNP chip was used for genotyping the ear tissue DNA of the experimental group. Subsequently, the association of phenotype data and genotype data was performed using Gemma-0.98.1 software. A linear mixed model was used for the association study. The results showed that four fleece traits were associated with 18 significant SNPs at the genome level and 232 SNPs at the chromosome level, through gene annotated from Capra hircus genome using assembly ARS1. A total of 107 candidate genes related to fleece traits were obtained. Combined with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we can find that CLNS1A , CCSER1 , RPS6KC1 , PRLR , KCNRG , KCNK9, and CLYBL can be used as important candidate genes for fleece traits of NXWCG. We used Sanger sequencing and suitability chi-square test to further verify the significant loci and candidate genes screened by GWAS, and the results show that the base mutations loci on the five candidate genes, CCSER1 (snp12579, 34,449,796, A → G), RPS6KC1 (snp41503, 69,173,527, A → G), KCNRG (snp41082, 67,134,820, G → A), KCNK9 (14:78472665, 78,472,665, G → A), and CLYBL (12: 9705753, 9,705,753, C → T), significantly affect the fleece traits of NXWCG. The results provide a valuable basis for future research and contribute to a better understanding of the genetic structure variation of the goat.
e18019 Background: To investigate the safety and efficacy of hypofractionated plus chemotherapy in patients with initially distant metastatic nasopharyngeal carcinoma (mNPC). Methods: Between May 2014 and June 2020, 35 patients initially diagnosed with mNPC were enrolled on prospective trial. The enrolled patients were assigned randomly to receive either hypofractionated plus chemotherapy (HFRT) or conventionally fractionated radiotherapy plus chemotherapy (CFRT). 60 Gy over 25 fractions was administered to the HFRT group (n = 17) and 69.96 Gy over 33 fractions was administered to the CFRT group (n = 18), both groups five times each week. Progression free survival (PFS) comprised the primary endpoint. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and acute and late toxicity comprised the secondary endpoints. Results: Twenty-eight patients (seven were excluded) were enrolled. The 2-year PFS was 33.3% (HFRT group) versus 30.0% (CFRT group) (stratified hazard ratio (HR):1.09; 95% confidence interval (CI): 0.45–2.65, P = .843). The 2-year OS was 66.7% (HFRT group) versus 62.5% (CFRT group) (stratified HR, 0.88; 95% CI; 0.31–2.51, P= .806). All patients experienced acute grade 1 or 2, skin toxicity, oral mucositis, dysphagia, dry mouth, but no acute grade 3 or 4 toxicities. All patients had grade 1 late xerostomia. Two patients experienced hearing loss (one grade 1 and one grade 3). One patient developed mucosal necrosis. Conclusions: The two groups had similar outcomes. Improving the balance between severe late toxicities and local control by appropriately reducing the total dose but increasing the fractionated dose has marked clinical significance for patients with initially diagnosed mNPC. The trial has been registered with clinicaltrials.gov (NCT03598218). Clinical trial information: NCT03598218 . [Table: see text]
Background. Lung metastasis of malignant tumor signifies worse prognosis and immensely deteriorates patients’ life quality. Spatholobi Caulis (SC) has been reported to reduce lung metastasis, but the mechanism remains elusive. Methods. The active components and corresponding targets of SC were obtained from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) database and the SwissTargetPrediction database. The disease targets were acquired from DisGeNET and GeneCards databases. Venn map was composed to figure out intersection targets by using R. The PPI network was constructed through STRING and Cytoscape, and MCODE plug-in was used to sift hub targets. Gene Ontology (GO)-Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out by utilizing clusterProfiler package (R3.6.1) with adjusted value <0.05. Network of SC-active components-intersection targets-KEGG pathway was accomplished with Cytoscape. Molecular docking between hub targets and active components was performed, analyzed, and visualized by AutoDockTools, AutoDock Vina, PLIP Web tool, and PYMOL. Results. 24 active components and 123 corresponding targets were screened, and the number of disease targets and intersection targets was 1074 and 47, respectively. RELA, JUN, MAPK1, MAPK14, STAT3, IL-4, ESR1, and TP53 were the 8 hub targets. GO analysis and KEGG analysis elucidated that SC could ameliorate lung metastasis mainly by intervening oxidative stress, AGE-RAGE signaling pathway, and microRNAs in cancer. All 8 hub targets were proven to combine successfully with active components of SC. Conclusion. Inflammation is the core factor that integrates all these targets, biological process, and signaling pathways, which indicates that SC prevents or reduces lung metastasis mainly by dispelling inflammation.
Cinobufotalin injection is a water-soluble preparation extracted from the skin secretion of Bufo bufo gargarizans Cantor or B. melanotictus Schneider, which has been widely used as an adjuvant treatment in lung cancer patients. This study aimed to evaluate the clinical efficacy and safety of cinobufotalin (PubChem CID: 259776) injection as an adjunctive treatment for lung cancer. We designed a meta-analysis that performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We aim to include randomized controlled trials by systematically searching the PubMed, EMBASE, CNKI, Wanfang database, VIP, CBM, the Cochrane Central Register of Controlled Trials, and Chinese Clinical Trial Registry from inception to Mar 1, 2020, comparing the difference between the use of cinobufotalin injection as an adjunctive treatment and a control group without cinobufotalin injection. The objective response rate (ORR) and quality of life (QOL) will be defined as the primary outcomes, and the disease control rate (DCR) and adverse events will be defined as the secondary outcomes. We included 21 articles with 1735 cases of lung cancer patients. Comparison results show that combining with cinobufotalin injection can improve ORR (OR = 1.77, 95% CI [1.43, 2.21], < 0.001), with low heterogeneity ( = 0.94, I2 = 0%); DCR (OR = 2.20, 95% CI [1.70, 2.85], < 0.001), with low heterogeneity ( = 0.60, I2 = 0%); KPS score (OR = 3.10, 95% CI [2.23, 4.32], < 0.001), with low heterogeneity ( = 0.85, I2 = 0%); and the effect of pain relief (OR = 2.68, 95% CI [1.30, 5.55], = 0.008), with low heterogeneity ( = 0.72, I2 = 0%). Low-to-moderate evidence shows that cinobufotalin injection combined with chemotherapy can significantly increase ORR, DCR, QOL, and the effect of pain relief. Meanwhile, cinobufotalin injection did not bring additional adverse events such as hematological toxicity, gastrointestinal toxicity, cardiotoxicity, hepatotoxicity, and nephrotoxicity; however, multicenter, large-sample, high-quality clinical research results are still needed to reveal the therapeutic effect of cinobufotalin injection in small-cell lung cancer (PROSPERO registration number: CRD42020170052).
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